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Molecular Pain 2023Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting...
Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating, treatment-limiting, side-effect of several classes of chemotherapy drugs. While negatively impacting oncology patients' quality of life, chemotherapy-induced large-fiber (LF) neuropathy is amongst the least well understood components of CIPN, and one for which there is currently no established therapy. Preliminary clinical observations have led to the suggestion that Duloxetine, which is used for the treatment of pain associated with small-fiber CIPN (SF-CIPN), may be effective against LF-CIPN. In the present experiments we developed a model of LF-CIPN and studied the effect of Duloxetine on LF-CIPN induced by two neurotoxic chemotherapy agents: the proteasome inhibitor, Bortezomib, a first-line treatment of multiple myeloma; and, the anti-microtubule taxane, Paclitaxel, used in the treatment of solid tumors. Since there are currently no models for selective the study of LF-CIPN, our first aim was to establish a pre-clinical model in the rat. LF-CIPN was evaluated with the Current Perception Threshold (CPT) assay, which uses a high frequency (1000 Hz) electrical stimulus protocol that selectively activates large-fiber myelinated afferents. Our second aim was to use this model to test the hypothesis that Duloxetine can prevent LF-CIPN. We report that Bortezomib and Paclitaxel induce elevation of CPT, compatible with loss of large-fiber function, which are prevented by Duloxetine. Our findings support the clinical observation that Duloxetine may be an effective treatment for the large-fiber CIPN. We also suggest that CPT could be used as a biomarker for LF-CIPN in patients receiving neurotoxic chemotherapy.
Topics: Rats; Animals; Paclitaxel; Duloxetine Hydrochloride; Bortezomib; Rats, Sprague-Dawley; Quality of Life; Peripheral Nervous System Diseases; Antineoplastic Agents
PubMed: 37338165
DOI: 10.1177/17448069231185694 -
Pain Practice : the Official Journal of... Nov 2023
Topics: Humans; Duloxetine Hydrochloride; Thiophenes
PubMed: 37309239
DOI: 10.1111/papr.13261 -
International Journal of Clinical... Feb 2024Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Although duloxetine has shown a positive effect on pain relief with hip and knee osteoarthritis, there is no pooled analysis of duloxetine for pain relief and opioid consumption in patients after total hip or knee arthroplasty.
AIM
This systematic review and meta-analysis aimed to analyze pain control, opioid consumption, and associated adverse events of perioperative administration of duloxetine after total hip or knee arthroplasty.
METHOD
After being registered with PROSPERO (CRD42022323202), the databases of MEDLINE, PubMed, Embase, Web of Science, Cochrane Library, and ClinicalTrials.gov were searched from inception until March 20, 2023, for randomized controlled trials (RCTs). Primary outcomes were the visual Analog Scale (VAS) pain scores at rest (rVAS) and upon ambulation (aVAS). Secondary outcomes were postoperative opioid consumption quantified as oral morphine milligram equivalents (MMEs) and adverse effects of duloxetine.
RESULTS
Nine RCTs with 806 cases were included. Duloxetine was associated with lower VAS scores at different times after surgery (24 h, two weeks, and ≥ 3 months). Compared to placebo, perioperative daily duloxetine use significantly reduced daily opioid MMEs at 24 h (standard mean deviation [SMD] -0.71, 95% confidence interval [95% CI] -1.19 to -0.24, P = 0.003), three days (SMD -1.10, 95% CI -1.70 to -0.50, P = 0.0003), and one week (SMD -1.18, 95% CI -1.99 to -0.38, P = 0.004) after surgery. The duloxetine group had a significantly lower rate of nausea (odds ratio 0.62, 95% CI [0.41 to 0.94], P = 0.02) and a higher rate of drowsiness and somnolence (odds ratio 1.87, 95% CI [1.13 to 3.07], P = 0.01) compared to the placebo group. No significant differences were observed in the rates of other adverse events.
CONCLUSION
Perioperative duloxetine significantly decreased postoperative pain and opioid consumption with good safety profiles. Further high quality designed and well-controlled randomized trials are warranted.
Topics: Humans; Analgesics, Opioid; Duloxetine Hydrochloride; Arthroplasty, Replacement, Hip; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37294475
DOI: 10.1007/s11096-023-01593-x -
Journal of Orthopaedic Surgery (Hong... 2023Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the... (Review)
Review
Duloxetine is a serotonin and norepinephrine reuptake inhibitor (SNRI) with clinical efficacy in chronic pain conditions. In this study, we aim to evaluate the analgesic effect and safety of duloxetine in total knee arthroplasty (TKA). A systematic search was completed on MEDLINE, PsycINFO, and Embase from inception to December 2022 to find relevant articles. We used Cochrane methodology to evaluate the bias of included studies. Investigated outcomes included postoperative pain, opioid consumption, adverse events (AEs), range of motion (ROM), emotional and physical function, patient satisfaction, patient-controlled analgesia (PCA), knee-specific outcomes, wound complications, skin temperature, inflammatory markers, length of stay, and incidence of manipulations. Nine articles involving 942 participants were included in our systematic review. Out of nine papers, eight were randomized clinical trials and one was a retrospective study. The results of these studies indicated the analgesic effect of duloxetine on postoperative pain, which was measured using numeric rating scale and visual analogue scale. Deluxetine was also effective in reducing the morphine requirement and wound complications and enhancing patient satisfaction after surgery. However, the results on ROM, PCA, and knee-specific outcomes were contraventional. Deluxetine was generally safe without serious AEs. The most common AEs included headache, nausea, vomiting, dry mouth, and constipation. Duloxetine may be an effective treatment option for postoperative pain following TKA, but further rigorously designed and well-controlled randomized trials are required.
Topics: Humans; Duloxetine Hydrochloride; Arthroplasty, Replacement, Knee; Retrospective Studies; Pain, Postoperative; Analgesics, Opioid; Randomized Controlled Trials as Topic
PubMed: 37279647
DOI: 10.1177/10225536231177482 -
Journal of Child and Adolescent... Jun 2023Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and... (Review)
Review
Childhood mental illness is an ongoing public health crisis which is accompanied by an increase in antidepressant (i.e., serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors) use in children. Recent evidence highlighting the cultural differences in the utilization, efficacy, and tolerability of antidepressants in children underscores the need for diverse samples in studies examining antidepressant use. Furthermore, the American Psychological Association in recent years has emphasized the importance of including participants from diverse backgrounds in research studies, including investigations of medication efficacy. The present study, therefore, examined the demographic composition of samples used and reported in antidepressant efficacy and tolerability studies with children and adolescents experiencing anxiety and/or depression in the last decade. A systematic literature review utilizing two databases was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. In line with the extant literature, antidepressants were operationalized as , , , , and Out of the 11 articles included in this review, 71% reported having a primarily adolescent sample (i.e., over 50% of the sample was 12 years or older). In addition, studies omitted any transgender, genderqueer, or gender-nonconforming demographics, and one study omitted all racial demographic information. While 64% of studies only partially reported racial demographic information, 36% of studies omitted ethnicity demographics altogether. The present study addresses a gap in the literature by supporting a lack of diversity in studies examining antidepressant use in children and adolescents. Furthermore, it underscores the importance of future studies using a more diverse and representative sample. Limitations of the present study included limited generalizability and the lack of independent and blind reviewer process. Possible explanations for the lack of inclusion and suggestions on how to address these disparities are discussed.
Topics: Child; Adolescent; Humans; Antidepressive Agents; Selective Serotonin Reuptake Inhibitors; Fluoxetine; Sertraline; Duloxetine Hydrochloride
PubMed: 37253162
DOI: 10.1089/cap.2022.0090 -
Pain Practice : the Official Journal of... Sep 2023Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
Duloxetine has been used as an adjunct in multimodal analgesia for acute postoperative pain in clinical studies. This meta-analysis aims to conclude whether oral duloxetine, when given perioperatively, is any better than a placebo in managing postoperative pain. Effects of duloxetine on postoperative pain scores, time to first rescue analgesia, postoperative rescue analgesia consumption, side effects attributable to duloxetine, and patient satisfaction profile were assessed.
METHOD
MEDLINE, Web of Science, EMBASE, Scholar Google, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched with keywords including "Duloxetine" AND "postoperative pain", "Duloxetine" AND "acute pain" and with "Duloxetine" till October 2022. This meta-analysis included randomized clinical trials in which perioperative duloxetine 60 mg per oral was administered not more than 7 days before surgery and for at least 24 after surgery but not more than 14 days after surgery. All RCTs in which the comparator is placebo and outcomes related to analgesic efficacy like pain scores, opioid consumption, and side effects of duloxetine until 48 h postoperatively were included. Data were extracted from the studies and a risk of bias summary was formed using the Cochrane Collaboration tool. Effect sizes were given as standardized mean differences for continuous outcomes and risk ratios (RR) by the Mantel-Haenszel test for the categorical outcome. Confirmation of publication bias was done by Egger's regression test (p < 0.05). If publication bias or heterogeneity was detected, the trim-and-fill method was used to calculate the adjusted effect size. Sensitivity analysis was done by leaving one out method after excluding the study with a high risk of bias. Subgroup analysis was done based on the type of surgery and gender. The study was prospectively registered in the PROSPERO under the registration number CRD42019139559.
FINDINGS
29 studies with 2043 patients met the inclusion criteria and were reviewed for this meta-analysis. Postoperative pain scores at 24 h [Std. Mean Difference (95% CI); -0.69 (-1.07, -0.32)] and at 48 h [-1.13 (-1.68, -0.58)] are significantly less with duloxetine (p-value < 0.05). Time to first rescue analgesia was significantly more in patients where duloxetine was administered [1.27 (1.10, 1.45); p-value > 0.05]. Opioid consumption up to 24 h [-1.82 (-2.46, -1.18)] and 48 h [-2.48 (-3.46, -1.50)] was significantly less (p-value < 0.05) in patients who received duloxetine. Complications and recovery profiles were similar in patients receiving either duloxetine or a placebo.
INTERPRETATION
Based on GRADE findings, we conclude that there is low to moderate evidence to advocate the use of duloxetine for managing postoperative pain. Further trials are needed to replicate or refute these results based on robust methodology.
Topics: Humans; Analgesics, Opioid; Pain Management; Duloxetine Hydrochloride; Randomized Controlled Trials as Topic; Pain, Postoperative
PubMed: 37246352
DOI: 10.1111/papr.13253 -
Drug Metabolism and Pharmacokinetics Aug 2023The objectives of this analysis were to characterize the pharmacokinetics of duloxetine in Japanese pediatric patients aged 9-17 years with major depressive disorder...
The objectives of this analysis were to characterize the pharmacokinetics of duloxetine in Japanese pediatric patients aged 9-17 years with major depressive disorder (MDD) and to explore potential intrinsic factors affecting its pharmacokinetics. A population pharmacokinetic (PK) model was developed with plasma steady-state duloxetine concentrations from Japanese pediatric patients with MDD in an open-label long-term extension trial in Japan (ClinicalTrials.gov Identifier: NCT03395353). Duloxetine pharmacokinetics in Japanese pediatric patients was well described by a one-compartment model with first-order absorption. The population mean estimates of CL/F and V/F of duloxetine were 81.4 L/h and 1170 L, respectively. Patient intrinsic factors were assessed for their potential influence on duloxetine apparent clearance (CL/F). Only sex was identified as a statistically significant covariate of duloxetine CL/F. Duloxetine pharmacokinetic parameters and model-predicted duloxetine concentrations at steady state in the Japanese pediatric population were compared with those in Japanese adults. The mean duloxetine CL/F in pediatrics is slightly higher than adults, it is, however, expected that comparable steady-state duloxetine exposure in pediatric patients can be achieved with the approved dose regimen for adults. The population PK model provides useful information to understand the pharmacokinetic characteristics of duloxetine for Japanese pediatric patients with MDD. CLINICALTRIALS.GOV IDENTIFIER: NCT03395353.
Topics: Adult; Child; Humans; Depressive Disorder, Major; Duloxetine Hydrochloride; East Asian People; Japan
PubMed: 37244205
DOI: 10.1016/j.dmpk.2023.100496 -
Clinical and Experimental Rheumatology Jun 2023To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM).
OBJECTIVES
To identify the predictive factors of treatment response to acupuncture in patients with fibromyalgia (FM).
METHODS
Patients with FM refractory to standard drug therapy underwent eight weekly acupuncture sessions. Significant improvement, defined as a reduction of at least 30% of the revised Fibromyalgia Impact Questionnaire (FIQR), was assessed at the end of the eight weeks (T1) of treatment and three months after the end of treatment (T2). Univariate analysis was conducted to identify predictors of significant improvement at T1 and T2. Variables that resulted to be significantly associated with clinical improvement at univariate analysis were included in multivariate models.
RESULTS
Analyses were conducted on 77 patients (9 males, 11.7%). At T1, significant improvement in FIQR was recorded in 44.2% of patients. At T2, persistent significant improvement was recorded in 20.8% of patients. In the multivariate analysis, predictive variables of treatment failure were tender point count (TPC) (odds ratio [OR] =0.49, 95% confidence interval [95% CI]: 0.28-0.86, p=0.01) and pain magnification (OR=0.68, 95% CI: 0.47-0.99, p=0.04) assessed with the Pain Catastrophising Scale, at T1. At T2, the only predictive variable of treatment failure was concomitant duloxetine use (OR=0.21, 95% CI: 0.05-0.95, p=0.04).
CONCLUSIONS
High TPC and a tendency for pain magnification predict immediate treatment failure, while duloxetine therapy predicts it three months after completion of the acupuncture course. The identification of clinical characteristics of unfavourable response to acupuncture could help to implement a cost-effective prevention of treatment failure in FM.
Topics: Male; Humans; Fibromyalgia; Duloxetine Hydrochloride; Pain; Acupuncture Therapy; Research Design
PubMed: 37223911
DOI: 10.55563/clinexprheumatol/1xr38b -
Zhejiang Da Xue Xue Bao. Yi Xue Ban =... Aug 2022To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis. (Meta-Analysis)
Meta-Analysis
OBJECTIVE
To evaluate the efficacy and safety of antidepressants in treatment of depression disorder in children and adolescents by network meta-analysis.
METHODS
Databases of PubMed, Cochrane Library, EMBASE, Web of Science, PsycINFO, CBM, CNKI and Wanfang Data were searched for randomized controlled trials (RCT) related to antidepressants in treatment of children and adolescents with depression from inception to December 2021. Quality assessment and data extraction from the included RCTs were performed. Statistical analyses of efficacy and tolerability were conducted with Stata 15.1 software. Surface under the cumulative ranking (SUCAR) was used to rank the value of the antidepressants.
RESULTS
A total of 33 RCTs were included in 32 articles, involving 6949 patients. There are 13 antidepressants used in total, including amitriptyline, vilazodone, fluoxetine, selegiline, paroxetine, imipramine, desipramine, sertraline, nortriptyline, escitalopram, citalopram, venlafaxine and duloxetine. The results of network meta-analysis showed that the efficacy of duloxetine ( =1.95, 95% 1.41-2.69), fluoxetine ( =1.73, 95% 1.40-2.14), venlafaxine ( =1.37, 95% 1.04-1.80) and escitalopram ( =1.48, 95% : 1.12-1.95) were significantly higher than that of placebos (all <0.05); the probability cumulative ranks were duloxetine (87.0%), amitriptyline (83.3%), fluoxetine (79.0%), escitalopram (62.7%), etc. The results showed that the intolerability of patients receiving imipramine ( =0.15, 95% 0.08-0.27), sertraline ( =0.33, 95% 0.16-0.71), venlafaxine ( =0.35, 95% 0.17-0.72), duloxetine ( =0.35, 95% 0.17-0.73) and paroxetine ( =0.52, 95% 0.30-0.88) were significantly higher than that of placebos (all <0.05), and the probability cumulative ranks were imipramine (95.7%), sertraline (69.6%), venlafaxine (68.6%), duloxetine (68.2%), etc. Conclusion: Among 13 antidepressants, duloxetine, fluoxetine, escitalopram and venlafaxine are significantly better than placebo in terms of efficacy, but duloxetine and venlafaxine are less well tolerated.
Topics: Adolescent; Child; Humans; Venlafaxine Hydrochloride; Duloxetine Hydrochloride; Fluoxetine; Sertraline; Paroxetine; Amitriptyline; Imipramine; Depression; Escitalopram; Network Meta-Analysis; Depressive Disorder, Major; Antidepressive Agents
PubMed: 37202104
DOI: 10.3724/zdxbyxb-2022-0145 -
BMC Musculoskeletal Disorders May 2023Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Chronic musculoskeletal pain (CMP) is a complex condition that is mainly treated with analgesic drugs. However, antidepressant intervention is also an important factor in the treatment of CMP. Duloxetine is an effective treatment option for patients with CMP as its antidepressant effect. The purpose of this article is to evaluate the efficacy and safety of duloxetine in treating CMP.
DATABASES AND DATA TREATMENT
We searched PubMed, Web of Science, Embase, Cochrane Library from inception to May, 2022. Randomized controlled trials (RCTs) evaluating the efficacy and safety of duloxetine versus placebo in patients with CMP were included. We identified 13 articles and studied a population of 4201 participants in 4 countries.
RESULTS
This meta-analysis showed that the duloxetine has statistically significant compared with the placebo control, benefits on 24-hour average pain, living quality, physical function, and global impressions and there was no difference in the incidence of serious adverse event. In general, duloxetine can improve mood and pain level at the same time.
CONCLUSIONS
This review shows a significant contribution of duloxetine to CMP symptom relief. This meta-analysis improved that duloxetine can significantly reduce the pain level of patients, improve depressive symptoms and global impression, and has no obvious serious adverse reactions. However, additional studies are required to confirm the relationship between psychological diseases and chronic pain and explore their internal links.
Topics: Humans; Duloxetine Hydrochloride; Musculoskeletal Pain; Analgesics; Chronic Pain; Antidepressive Agents
PubMed: 37198620
DOI: 10.1186/s12891-023-06488-6